We propose to assess the oncogenic risk of ultrasound, using the C3H/10T1/2 in vitro assay for malignant transformation. This assay is a more direct and quantitative measure of oncogenic risk than are assays of mutation or chromosomal alterations. Pulsed ultrasonic beams configured to simulate diagnostic conditions will be used to irradiate cells alone, in combination with carcinogenic treatment, or followed by post-treatment culturing in 0.1 /g/ml of 12-0-tetradecanoyl-phorbol-13-acetate (TPA) in order to investigate the possible oncogenic interaction of co-stressors and tumor promotors with ultrasound. In examining the effect of ultrasound alone, experiments will be designed to detect a malignant transformation rate equivalent to or greater than the response of 1 Gy of 250 kVp X-rays or to about 2 /g/ml of benzo(a)pyrene, with 95% statistical confidence above the spontaneous transformation rate. In examining the effect of ultrasound as a co-stressor, experiments will be designed to detect a two-fold enhancement of transformation by ultrasound with 95% statistical confidence. Cells will be insonated in suspension in a transmission chamber at 37 degrees C using uniform, minimally focussed beam profiles, with insonation parameters simulating the upper range of pressure amplitudes from clinical ultrasonic imaging and doppler systems. Emphasis will be placed on providing replicable, well-characterized ultrasound delivery and bioassay.